This Tutorial Review presents an overview on the synthesis, characterization and applications of metal complexes containing curcumin (=1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) and ...its derivatives as ligands. Innovative synthetic strategies leading to soluble and crystallizable metal curcumin complexes are outlined in detail. Special emphasis is placed on the highly promising and exciting medicinal applications of metal curcumin complexes, with the three most important areas being anticancer activity and selective cytotoxicity, anti-Alzheimer's disease activity, and antioxidative/neuroprotective effects. Overall, this Tutorial Review provides the first general overview of this emerging and rapidly expanding field of interdisciplinary research.
Finerenone is a novel non-steroidal mineralocorticoid receptor (MR) antagonist (MRA) with high binding affinity, high MR selectivity and a short plasma half-life. In two major endpoint-driven ...clinical trials in patients with chronic kidney disease and type 2 diabetes mellitus (FIDELIO-DKD and FIGARO-DKD), finerenone induced significant cardiorenal protective actions, and has been recently approved for treatment of these patients. Heart failure with preserved ejection fraction (HFpEF) is a devastating clinical syndrome with increasing prevalence and poor prognosis. Pharmacological therapy of HFpEF is very limited and new therapeutic options are urgently needed. Finerenone has been shown to improve multiple pathophysiological parameters of HFpEF in preclinical models. In consonance, pre-specified subgroup analyses of FIDELIO-DKD and FIGARO-DKD suggested a potential beneficial effect of finerenone in HFpEF. This review will discuss the pharmacodynamic and -kinetic profile of finerenone. We will provide a general overview over the complex pathophysiology of HFpEF and data from pre-clinical studies, focusing on how finerenone improves multiple components of this pathophysiology. Finally, we will discuss current and future clinical trials with finerenone in heart failure patients focusing on HFpEF.
•New solvent-free dibenzyl complexes Ln(CH2Ph)2n (Ln = Eu, Sm, Yb) were isolated.•The first first lanthanide-cyclobutadienyl complexes have been prepared.•The quest for even better single-molecule ...magnets continued in 2018.•Unique heterobimetallic Sm/Co polyarsenides and Sm polystibides were prepared.•The synthesis of the first Np(II) organometallic complex was achieved.
This review summarizes the progress in organo-f-element chemistry during the year 2018. A continuing trend for many years, which remained important in 2018, was the synthesis and investigation of reactive trivalent lanthanide mono- and bis(alkyl) or (benzyl) complexes supported by a variety of non-cyclopentadienyl ligands such as amidinates, β-diketiminates or NHC ligands. An important contribution was the synthesis of the homoleptic, solvent-free dibenzyl complexes Ln(CH2Ph)2n (Ln = Eu, Sm, Yb) which served as precursors for the synthesis of the first divalent lanthanide imides (THF)Ln(μ3-NDipp)4. Lanthanide carbene chemistry has also been of growing interest. Functionalized NHC ligands were employed to unveil new reactivity as demonstrated in the synthesis of homoleptic lanthanide complexes with aryloxide-tethered NHC ligands, Ln(LR)3 (LR = 2-O-3,5-tBu2C6H2(1-C{N(CH)2N(R)}), R = iPr, tBu, Mes), which reacted with CO2 by selective insertion into Ln–C(NHC) bonds. A diverse reactivity towards small unsaturated molecules was observed for phosphino and thiophosphinoyl alkylidene lanthanide complexes as well as for phosphinidene lanthanide complexes. Furthermore, the trinuclear mixed oxo/alkyl complexes L13Ln3(μ2-CH3)3(μ3-CH3)(μ3-O) (with L1 = PhC(NC6H3iPr2-2,6)2; Ln = Sc, Y, Lu, Dy) undergo non-redox oxygen transfer with PhNCS or CS2 despite the presence of reactive Ln-alkyl bonds. The synthesis of pseudo-Grignard reagents PhLnI (Ln = Eu, Yb) was investigated and their synthetic potential in organometallic chemistry demonstrated. The first lanthanide-cyclobutadienyl complexes were obtained as anionic “tuck-in” complexes M{η4-C4(SiMe3)4}{η4-C4(SiMe3)3-κ-(CH2SiMe2)}2− (Ln = Y, Dy), showing square-shaped cyclobutadienyl ligands. Further progress has been made in the understanding of “new” divalent lanthanide chemistry, especially the influence of the ligand size. The small CpMe ligand formed highly reactive complexes, e.g. K(crypt)Y(CpMe)3, with the larger lanthanides, which reacted with the solvent to give unprecedented reductive THF-ring opening. However, with smaller lanthanides the complexes (18-crown-6)K(μ-CpMe)K(18-crown-6)CpMe3Ln (Ln = Tb, Ho), displaying an inverse sandwich as counter-cation, could be isolated. The reactivity of the highly bulky complex SmCpAr-Et2 (CpAr-Et = C5(4-EtC6H4)5) towards a large range of small molecules was investigated, revealing only reaction with cuminil to afford the first trivalent lanthanide decaaryllanthanidocene complex SmCpAr-Et2(Ar′C(O)C(O)Ar′) (Ar′ = 4-iPrC6H4). Following the important discovery of recent years on SMM (single molecule magnet) behavior of Dy metallocenes, the quest for even better SMMs continued in 2018. Several new record-holding complexes were synthesized based on polyisopropyl-cyclopentadienyl complexes, with the best complex to date being (C5iPr5)(C5Me5)Dy BAr4, showing magnetic hysteresis up to 80 K and an effective energy barrier to reversal of magnetization Ueff = 1541 cm−1.
Several remarkable lanthanide arene complexes have been prepared and structurally characterized. For example, the bimetallic inverse sandwich La2+ complex salt K(18-crown-6)(THF)2(Cp″2La)2(μ-η6:η6-C6H6)·THF (Cp″ = C5H3(SiMe3)2-1,3) reduces hydrocarbons such as naphthalene, anthracene, or cyclooctatetraene to give La3+ complexes of the hydrocarbon anions. Samarium-arene bonding has also been observed in the rare samarium(II) aryloxide Sm(OAriPr6)2 AriPr6 = −C6H3-2,6-(C6H2-2,4,6-iPr3)2 and in the remarkable tetranuclear samarium(II) inverse sandwich complex (µ-η6:η6-C7H8)KSmL32 (L = OSi(OtBu)3). Several new triple-decker complexes of the type Ln2(COT″)3 (COT″ = bis(trimethylsilyl)cyclooctatetraenyl dianion) have been isolated and structurally characterized. The synthesis and structural characterization of four unsolvated divalent lanthanide cyclononatetraenyl sandwich complexes, Ln(Cnt)2 (Ln = Sm, Eu, Tm, Yb; Cnt = η9-cyclononatetraenyl) have also been achieved. Single-crystal X-ray diffraction studies revealed that these neutral sandwich complexes are rigorously linear. A rare heterobimetallic 1 ferrocenophane terbium(III) complex has been found to exhibit single-ion magnet behavior. Reduction of the scandium precursor Sc(nacnac)(OAr)(OCP) (nacnac– = ArNC(CH3)2CH, Ar = 2,6-iPr2C6H3) with KC8 afforded a binuclear scandium complex comprising a unique OCPPCO4− central motif formed through P–P radical coupling. Heterobimetallic Sm/Co polyarsenides (CptttCo)2As4Sm(C5Me4R)2 (Cpttt = 1,2,4-C5H2tBu3, R = Me, nPr) were synthesized from the reaction of divalent Sm complexes Cp*2Sm, Cp*2Sm(THF)2 or (C5Me4nPr)2Sm with (CptttCo)2(μ,η2:2-As2)2, while the Sm/Sb multimetallic complex (Cp*2Sm)4(μ4,η2:2:2:2-Sb8) was synthesized from the oxidation of Cp*2Sm with activated antimony. The chemistry of endohedral lanthanide metallofullerenes continued to be an active field of research in 2018. Significant achievements have also been made in the area of organolanthanide catalysis. For example, a variety of highly active lanthanide catalysts for the polymerization of polar substituted styrene monomers as well as the polymerization of 2-vinylpyridine have been developed. Half-sandwich complexes of scandium have been successfully employed in the copolymerization of myrcene with ethylene and propylene. New organolanthanide-catalyzed reactions include the diastereo- and enantioselective C(sp)–H addition of terminal alkynes to 3,3-substituted cyclopropenes and the catalytic hydrothiomethylation of olefins and dienes with a series of methyl-alkyl sulfides. Moreover, the first-time scandium-catalyzed C(sp3)–H alkylation of N,N-dimethyl anilines with olefins has been investigated. Significantly less results over previous years have been published in 2018 on the use of organolanthanide precursors in materials science.
The synthesis and reactivity of complexes with actinide-element multiple bonds, e.g. AcC, AcN, AcP, is a highly active research area. The synthesis of uranium(IV) silyl-phosphino-carbene complexes was reported, among which the bis(carbene) complex U{C(SiMe3)(PPh2)}(BIMPTMS)(µ-Cl)Li(TMEDA)(µ-TMEDA)0.52 (36%) showing a 3-center U–C–P character and a short UCcarbene bond. A rare U(IV) imido species K(THF)3(PN)U(NH)(iPr2P(C6H3Me)N(C6H2Me2CH2) was isolated, in which one of the PN ligands has been cyclometallated. This complex was proposed to have been formed by the addition of the ligand C–H of a nearby methyl group to a uranium nitride intermediate. The synthesis and the diverse reactivity of the first base-free terminal phosphinidene thorium(IV) complex, Th(CptBu3)2(PR), towards heterounsaturated small molecules was reported. The functionalization of CO and tert-butyl nitrile have been reported for a Th(IV) bis(phosphido) complex, (C5Me5)2Th{P(Mes)(H)}2, involving intramolecular proton transfer reactions. The synthesis and characterization of the first Np(II) organometallic complex K(crypt)Np(Cp″)3 (crypt = 2,2,2-cryptand, Cp″ = C5H3(SiMe3)2) was achieved by reduction of a trivalent precursor. The synthesis and characterization of a neutral U(II) complex, U(NHAriPr6)2, and the very reactive uranium(III) cation U(NHAriPr6)2BArF24 supported by an amido bis(arene) ligand was reported. Good progress has been made in metallofullerene chemistry of the actinides, as evidenced by the structural characterization of the dimetallic actinide endohedral metallofullerene (EMF) U2@C80, revealing short U–U bonding inside the cage. Actinide complexes have also found new applications in catalysis, as shown by the first example of selective hydroboration of aldehydes and ketones using actinide catalysis.
The new PPA ligands 3‐5‐methyl‐3‐(trifluoromethyl)‐1H‐pyrazol‐1‐ylpropanamide (CF3MePPA; 3) and 3‐3,5‐bis(trifluoromethyl)‐1H‐pyrazol‐1‐ylpropanamide ((CF3)2PPA; 4) were synthesized by Aza‐Michael ...addition of the specific pyrazole derivatives to acrylamide. Both products were characterized by elemental analyses, IR and NMR spectroscopy, and mass spectrometry. X‐Ray structure determination of 3 revealed the presence of a one‐dimensional hydrogen‐bonded structure in the solid state. The ligating ability of the new ligands towards PdCl2 was studied, showing that 3 behaves similar to Me2PPA and reacts cleanly with PdCl2 to afford the sparingly soluble complex PdCl2(CF3MePPA‐κN)2. By contrast, the donor ability of pyrazolyl group in 4 was found to be considerably reduced, thus resulting in the formation of the unusual complex PdCl2{(CF3)2PPA‐κN}{(CF3)2PPA‐κO}.
The blood‐red plutonocene complex Pu(1,3‐COT′′)(1,4‐COT′′) (4; COT′′=η8‐bis(trimethylsilyl)cyclooctatetraenyl) has been synthesized by oxidation of the anionic sandwich complex LiPu(1,4‐COT′′)2 (3) ...with anhydrous cobalt(II) chloride. The first crystal structure determination of an organoplutonium(IV) complex revealed an asymmetric sandwich structure for 4 where one COT′′ ring is 1,3‐substituted while the other retains the original 1,4‐substitution pattern. The electronic structure of 4 has been elucidated by a computational study, revealing a probable cause for the unexpected silyl group migration.
The neutral plutonium(IV) sandwich complex Pu(1,3‐COT′′)(1,4‐COT′′) (COT′′=η8‐bis(trimethylsilyl)cyclooctatetraenyl) was synthesized and characterized by single‐crystal X‐ray diffraction. The asymmetric sandwich structure contains one 1,3‐ and one 1,4‐substituted COT′′ ring. The electronic structure of the compound was elucidated computationally, revealing a likely cause for silyl group migration.
The purpose of this study was to analyze the potential usefulness and clinical relevance of adding left atrial (LA) strain to left atrial volume index (LAVI) in the detection of left ventricular ...diastolic dysfunction (LVDD) in patients with preserved left ventricular ejection fraction (LVEF).
Recent studies have suggested that LA strain could be of use in the evaluation of LVDD. However, the potential utility and clinical significance of adding LA strain to LAVI in the detection of LVDD remains uncertain.
Using 2-dimensional speckle-tracking echocardiography, we analyzed a population of 517 patients in sinus rhythm at risk for LVDD such as those with arterial hypertension, diabetes mellitus, or history of coronary artery disease and preserved LVEF.
In patients with LV diastolic alterations and estimated elevated LV filling pressures, the rate of abnormal LA strain was significantly higher than an abnormal LAVI (62.4% vs. 33.6%, p < 0.01). In line with this, in patients with normal LAVI, high rates of LV diastolic alterations and abnormal LA strain were present (rates 80% and 29.4%, respectively). In agreement with these findings, adding LA strain to LAVI in the current evaluation of LVDD increased significantly the rate of detection of LVDD (relative and absolute increase 73.3% and 9.9%; rate of detection of LVDD: from 13.5% to 23.4%; p < 0.01). Regarding the clinical relevance of these findings, an abnormal LA strain (i.e., <23%) was significantly associated with worse New York Heart Association functional class, even when LAVI was normal. Moreover, in a retrospective post hoc analysis an abnormal LA strain had a significant association with the risk of heart failure hospitalization at 2 years (odds ratio: 6.6 95% confidence interval: 2.6 to 16.6) even adjusting this analysis for age and sex and in patients with normal LAVI.
The findings from this study provide important insights regarding the potential usefulness and clinical relevance of adding LA strain to LAVI in the detection of LVDD in patients with preserved LVEF.
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A series of heteroleptic tris(cyclopentadienyl) CeIV complexes has been isolated and crystallographically characterized, revealing the broad accessibility of such organocerium(IV) compounds. The ...oxidation of complexes CpMe3Ce(thf) and Cp′3Ce(thf) (CpMe=C5H4Me, Cp′=C5H4SiMe3), bearing monosubstituted electron‐poor cyclopentadienyl ligands, with 0.5 equivalents of 1,4‐benzoquinone or C2Cl6 gave the cerium(IV) hydroquinolate complexes CpMe3Ce(OC6H4O)CeCpMe3 and Cp′3Ce(OC6H4O)CeCp′3, or the chloride complexes CpMe3CeCl and Cp′3CeCl, respectively; the iodide complex Cp′3CeI was obtained from the reaction of Cp′3Ce(thf) with elemental iodine. The behavior of Cp′3CeCl in salt metathesis protocols employing alkali metal amides or alkyl, alkoxide, and aryloxide reagents was investigated, which gave rise to the robust and isolable cerium(IV) alkoxide Cp′3Ce(OtBu). Trivalent Cp′2CeCl2 was synthesized by AlMe4→Cl exchange utilizing Cp′2Ce(AlMe4) and AlMe2Cl. The reactivity of Cp′2CeCl2 towards the oxidants Ph3CCl, C2Cl6, 1,4‐benzoquinone, and I2 has been assessed, and has provided useful information on CeIII/CeIV redox deactivation pathways. In addition to X‐ray structure analysis, all the complexes were characterized by NMR, DRIFT (diffuse reflectance IR Fourier transform), and UV/Vis spectroscopy as well as elemental analysis. The tetravalent compounds were further analyzed for their magnetic susceptibility by using Evans’ method.
Organocerium complexes: Tris(cyclopentadienyl) scaffolds provide broad access to tetravalent organocerium complexes. The application of a diverse set of oxidants gives new insights into the oxidizability of homo‐ and heteroleptic cyclopentadienyl cerium(III) compounds (see scheme). All new compounds have been characterized by spectroscopy and X‐ray diffraction.
In this contribution, the first amidinate and amidine derivatives of
-carborane are described. Double lithiation of
-carborane (
) with
-butyllithium followed by treatment with ...1,3-diorganocarbodiimides, R-N=C=N-R (R =
Pr, Cy (= cyclohexyl)), in DME or THF afforded the new
-carboranylamidinate salts
-C
H
B
C(N
Pr)
Li(DME)
(
) and
-C
H
B
C(NCy)
Li(THF)
(
). Subsequent treatment of
and
with 2 equiv. of chlorotrimethylsilane (Me
SiCl) provided the silylated neutral bis(amidine) derivatives
-C
H
B
C{
PrN(SiMe
)}(=N
Pr)
(
) and
-C
H
B
C{CyN(SiMe
)}(=NCy)
(
). The new compounds
and
have been structurally characterized by single-crystal X-ray diffraction. The lithium carboranylamidinate
comprises a rare trigonal planar coordination geometry around the lithium ions.
Bis(demethoxy)curcumin (BDMC), extracted from rhizomes of the traditional herb Curcuma longa, has revealed a wide range of medicinal applications, such as antimicrobial and anticarcinogenic. Pure ...BDMC was obtained by recrystallization from ethanol and three BDMC solvates were identified with acetone, methanol, and isopropanol. The crystal structures of pure BDMC and the solvates were resolved by single crystal X-ray diffraction. Analyses of the crystal structures and calculations of crystal packing efficiencies revealed that pure BDMC is efficiently packed. The solvents involved are not utilized to fill the void spaces in the crystal structures, but to provide effective intermolecular interactions. The stoichiometry of the three solvates obtained from single crystal data is 1:1, which is in good agreement with the gravimetric analyses. Furthermore, the desolvation process and the stability of the solvates were investigated by various analytical techniques including X-ray diffraction, differential scanning calorimetry, thermogravimetric analyses, hot-stage microscopy, and dynamic vapor sorption. Results show that the methanol solvate is more stable compared to the acetone and isopropanol solvates attributed to the strong hydrogen bonding network. Moreover, the desolvation process of the three solvates proceeds through a destructive–reconstructive mechanism.
The reaction of Cu(NO
3
)
2
·3H
2
O with a potentially bidentate P,N-donor ligand, diphenyl-2-pyridylphosphine (PPh
2
Py), in 1:2 molar ratio resulted in formation of a κ
2
N,O-chelated complex, Cu(κ
...2
N,O-P(O)Ph
2
Py)
2
(NO
3
)
2
(1). A single-crystal X-ray study confirmed the formation of a five-membered κ
2
N, O-chelate involving pyridyl nitrogen and phosphine oxide oxygen donor sites. A DFT study was carried out on 1 to understand the chelate ring expansion process upon oxidation with PPh
2
Py. DFT analysis revealed that 1 contains a relatively strong M-N bond compared to its M-P bond, facilitating the oxidation of the P atom followed by chelate ring expansion.
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